Pharmacokinetics, safety, and tolerability of intravenous brivaracetam in pediatric patients with epilepsy: An open-label trial.

Abstract

ObjectiveTo evaluate the pharmacokinetics, safety, and tolerability of brivaracetam (BRV) as 15‐min intravenous (IV) infusion and bolus (≤2‐min injection).MethodsEP0065 (ClinicalTrials.gov: NCT03405714) was a Phase 2, multicenter, open‐label trial in patients ≥1 month to <16 years of age with epilepsy. Patients received up to 5 mg/kg/day BRV (not exceeding 200 mg/day). Enrollment was sequential by descending age, depending on safety review. Outcomes included BRV plasma concentrations before and after IV administration, treatment‐emergent adverse events (TEAEs), and discontinuations due to TEAEs.ResultsFifty patients were enrolled, received BRV, and completed the trial. Twenty‐six patients (52.0%) received 15‐min infusions and 24 (48.0%) received bolus injections. Most patients (80.0%) received one IV dose. In the 15‐min infusion group, geometric mean (GeoMean) BRV concentrations 15 (±2) min (n = 21) and 3 h (±15 min) (n = 21) post dose were 1903.0 ng/mL (geometric coefficient of variation [GeoCV]: 60.7%) and 1130.3 ng/mL (58.8%), respectively. In the bolus group, GeoMean BRV concentrations 15 (±2) min (n = 19) and 3 h (±15 min) (n = 21) post dose were 1704.8 ng/mL (GeoCV: 74.5%) and 1383.9 ng/mL (85.0%), respectively. Overall, 14 patients (28.0%) had TEAEs (15‐min infusion: 8 [30.8%]; bolus: 6 [25.0%]), most commonly (≥5% of patients) somnolence (3 [6.0%]). Ten patients (20.0%) had drug‐related TEAEs (15‐min infusion: 6 [23.1%]; bolus: 4 [16.7%]). No patients discontinued due to TEAEs, and no deaths occurred.SignificanceIV BRV (up to 200 mg/day) was well tolerated in patients ≥1 month to <16 years of age, regardless of whether BRV was administered as 15‐min infusion or bolus. No unexpected safety or pharmacokinetic differences were observed between patients receiving 15‐min infusions or bolus, and plasma concentrations were in the expected range. Safety results were consistent with the known safety profile of oral BRV, with no new safety concerns identified.